White matter hyperintensity (WMH) has been regarded as one of the major contributor of the vascular hypothesis of late-life depression (LLD) and cognitive decline in the elderly. On the other hand, cognitive reserve (CR) has long been hypothesized to provide resilience and adaptability against age- and disease-related insults. This study examined the role of CR, using proxy of education, in moderating the association between WMH and clinical LLD expression. A total of 54 elderly diagnosed with

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... ajor depressive disorder and 38 matched healthy controls participated in this study. They received MRI scanning and a battery of neuropsychological tests. WMH was quantified by an automated segmentation algorithm. Linear regression analyses were conducted separately in the LLD and control groups to examine the effects of WMH, education and their interaction in depression severity and various cognitive domains. WMH was significantly and negatively associated with executive function only in the healthy controls. In patients with LLD, we observed a significant interactive effect in education on the association between WMH and depression severity and language domain (category fluency task). Specifically, those with high education showed less depressive symptoms and cognitive decline as WMH increased. WMH is associated with lower cognitive function. However, in patients with LLD, high education attenuates the deleterious effect of WMH on mood and cognition. Therefore, CR appears to exert a protective effect on neurocognitive functioning in people with LLD.